DNA replication stress drives fragile site instability

Michal Irony-Tur Sinai, Batsheva Kerem*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


DNA replication stress is one of the early drivers enabling the ongoing acquisition of genetic changes arising during tumorigenesis. As such, it is a feature of most pre-malignant and malignant cells. In this review article, we focus on the early events initiating DNA replication stress and the preferential sensitivity of common fragile sites (CFSs) to this stress. CFSs are specific genomic regions within the normal chromosomal structure, which appear as gaps and breaks in the metaphase chromosomes of cells grown under mild replication stress conditions. The main characteristics predisposing CFSs to instability include late replication timing, delayed replication completion, failure to activate additional origins, origin paucity along large genomic regions, collision between replication and transcription complexes along large genes, and the presence of AT-dinucleotide rich sequences. The contribution of these features to instability at CFSs during early cancer development is discussed.

Original languageAmerican English
Pages (from-to)56-61
Number of pages6
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
StatePublished - Mar 2018

Bibliographical note

Publisher Copyright:
© 2017 Elsevier B.V.


  • Chromosomal instability
  • Common fragile sites
  • Replication stress


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